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Heart Failure Protein
January 20, 2000
image: American Heart Association

When comedian/talk show host David Letterman went into the hospital last week, he joined the more than 300,000 Americans who undergo cardiac surgery each year. Like them, he risked the sudden heart failure that commonly strikes after heart operations. But researchers at Johns Hopkins University and Queen’s University in Ontario have just discovered what causes the condition, and are working on new ways to treat it.

Stunning News

Nearly 90% of the patients who undergo heart surgery experience weakened heartbeat afterward, known as myocardial stunning. It can last from a matter of hours to several days, according to Dr. Anne Murphy, associate professor of pediatric cardiology at Johns Hopkins University School of Medicine. "It’s the reason heart patients must spend an entire day in intensive care following surgery," says Dr. Eduardo Marban, the cardiac physiologist who led the research. Myocardial stunning extracts a high price, not just because of the estimated $10 billion spent in post-operative patient care in the U.S., but also in terms of the emotional distress it causes the patients and their families.

Animated colored image of heart
The flow of oxygen-rich blood to the heart is interrupted, causing changes within heart cells.
image: American Heart Association

After 14 years of research, a study published in the journal Science shows what causes this dangerous condition. It originates in damage to molecules called Troponin I (pronounced "eye") which are vital to heart function.

"Troponin I is a protein that is very important to the process of muscle contracting," says Dr. Murphy. "It controls how the heart muscle responds to the signal for contraction and it’s very important for regulating the force of the heart muscle."

When a person has a heart attack or cardiac surgery, the flow of oxygen-rich blood to the heart is interrupted. This causes an increase in calcium levels, which in turn activates proteins called proteases. It’s the proteases that damage the Troponin I by shortening it, according to researchers. Although researchers had already established that there was some sort of link between myocardial stunning and Troponin I, this is first time they’ve demonstrated the problem at the molecular level.

Of Mice and Men

Dr. Anne Murphy
Colleague with Dr. Anne Murphy
By cloning genes for abnormal human Troponin I and inserting them into mice, researchers were able to observe its effects: The mice developed enlarged hearts, a sign of weakened heart muscle. "The force their heart muscles exerted was also far below normal," says Dr. Murphy. "The mice resembled humans with cardiac stunning in any way we could measure."

The damage to Troponin I not only explains why some patients become so sick after heart surgery, it also paves the way for new treatments. Although no specific new treatments have been developed yet, scientists are already at work on the problem. "We’re using these mice that we created and are starting to do new therapies and new approaches so that we can treat our patients better in the future," says Dr. Murphy. The hope is to eventually find ways to minimize cell damage or avoid it altogether, according to Dr. Marban.

Elsewhere on the Web

American Heart Association

American College of Cardiology

National Heart, Lung, and Blood Institute

National Heart Attack Alert Program

Heart Information Network



by STN2


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